Takatsugu Okegawa

The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction

The coxsackievirus and adenovirus receptor (CAR) mediates viral attachment and infection, but its physiologic functions have not been described. In nonpolarized cells, CAR localized to homotypic intercellular contacts, mediated homotypic cell aggregation, and recruited the tight junction protein ZO-1 to sites of cell–cell contact. In polarized epithelial cells, CAR and ZO-1 colocalized to tight junctions and could be coprecipitated from cell lysates. CAR expression led to reduced passage of macromolecules and ions across cell monolayers, and soluble CAR inhibited the formation of functional tight junctions. Virus entry into polarized epithelium required disruption of tight junctions. These results indicate that CAR is a component of the tight junction and of the functional barrier to paracellular solute movement. Sequestration of CAR in tight junctions may limit virus infection across epithelial surfaces.

Prognostic Significance of Circulating Tumor Cells in Patients With Hormone Refractory Prostate Cancer

PURPOSE Using the CellSearch System we evaluated whether circulating tumor cells predict survival in patients with hormone refractory prostate cancer. MATERIALS AND METHODS Circulating tumor cells were counted with the CellSearch System in whole blood. This system was developed using epithelial cell adhesion prostate cancer antibody based, immunomagnetic capture and automated staining methodology. Blood samples from 64 patients with hormone refractory prostate cancer were analyzed. RESULTS A threshold of 5 or more circulating tumor cells per 7.5 ml blood was used to evaluate the ability of circulating tumor cells to predict survival. Patient charts were retrospectively examined to determine median overall survival, which was 4 to 27 months (mean +/- SD 14.3 +/- 4.2, median 12.1). Of the 64 patients 32 (50%) had 5 or more circulating tumor cells with a median overall survival of 13.0 months compared with 20.0 months in patients with fewer than 5 (p <0.001). Circulating tumor cells and prostate specific antigen doubling time were significant parameters predicting overall survival on univariate and multivariate analyses. Overall survival in cases that converted from increased to nonincreased circulating tumor cell levels was longer than in cases that converted from nonincreased to increased levels after initiating the circulating tumor cell assay (p = 0.026). CONCLUSIONS In this study 5 or more circulating tumor cells in 7.5 ml blood was associated with survival in patients with hormone refractory prostate cancer. Circulating tumor cells may be an independent predictor of overall survival in patients with hormone refractory prostate cancer but they may also complement prostate specific antigen.

DETECTION OF MICROMETASTATIC PROSTATE CANCER CELLS IN THE LYMPH NODES BY REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION IS PREDICTIVE OF BIOCHEMICAL RECURRENCE IN PATHOLOGICAL STAGE T2 PROSTATE CANCER.

PURPOSE We evaluated whether detecting prostate cancer cells by the nested reverse transcriptase-polymerase chain reaction (RT-PCR) in lymph nodes has predictive value for serum prostate specific antigen (PSA) recurrence in patients undergoing radical prostatectomy. MATERIALS AND METHODS We assessed the presence of prostate cancer cells by RT-PCR for prostate specific membrane antigen and PSA assay in lymph nodes dissected from 38 patients with localized prostate cancer treated with radical prostatectomy. The results of nested RT-PCR assay were compared with biochemical recurrence. RESULTS Nested RT-PCR was positive in the lymph nodes of 2 of 18 patients (11%) with stage pT2a and 5 of 20 (25%) with stage pT2b disease. All 7 patients had biochemical recurrence. We noted a significant difference in the Kaplan-Meier recurrence-free actuarial probability curve in those with positive and negative nested RT-PCR results for prostate specific membrane antigen, PSA and prostate specific membrane antigen-PSA in the lymph nodes (p = 3.02x10(-7), 2.23x10(-7) and 3.02x10(-7), respectively). Multivariate analysis of serum PSA, Gleason score and preoperative RT-PCR assay in peripheral blood showed that nested RT-PCR for prostate specific membrane antigen, PSA and prostate specific membrane antigen-PSA in the lymph nodes were independent predictors of recurrence (p = 0.0089, 0.0075 and 0.0089, respectively). CONCLUSIONS Nested RT-PCR of the lymph nodes may be a useful pretreatment prognostic test for patients undergoing radical prostatectomy. Further research is necessary using a much larger number of patients with a longer followup.

Immunomagnetic Quantification of Circulating Tumor Cells as a Prognostic Factor of Androgen Deprivation Responsiveness in Patients With Hormone Naive Metastatic Prostate Cancer

PURPOSE We determined whether circulating tumor cells predict prostate specific antigen failure in patients with metastatic prostate cancer before endocrine therapy and compared their prognostic ability with other clinical factors. MATERIALS AND METHODS Circulating tumor cells were enumerated with the CellSearchtrade mark system in whole blood. This system was developed using epithelial cell adhesion molecule antibody based immunomagnetic capture and automated staining methodology. Prostate cancer cell lines (PC3, LNCaP, DU145) and mixed blood from healthy men were analyzed using this system. Blood samples from 80 patients with metastatic prostate cancer before endocrine therapy were analyzed. Circulating tumor cells were then assessed every 3 months after endocrine therapy in these patients. RESULTS Circulating tumor cell assay accuracy and reliability were determined using prostate cancer cell line (PC3, LNCaP, DU145) spiking experiments, which demonstrated a strong linear correlation (r = 0.99) and a constant recovery rate of 69% +/- 3%, 95% +/- 3% and 89% +/- 2%, respectively. The number of circulating tumor cells found ranged from 0 to 222 per 7.5 ml blood (mean 17 +/- 31, median 14). A threshold of 5 or more circulating tumor cells per 7.5 ml blood was used to evaluate the ability of circulating tumor cells to predict androgen deprivation responsiveness. Of the 80 patients 44 (55%) had 5 or more circulating tumor cells with a median androgen deprivation responsiveness of 17 months compared to more than 32 months for those with fewer than 5 circulating tumor cells (p = 0.007). The presence of circulating tumor cells, nadir prostate specific antigen values and Gleason score were significant parameters predictive of androgen deprivation responsiveness on univariate and multivariate analyses. CONCLUSIONS In this study the presence of 5 or more circulating tumor cells in 7.5 ml blood was associated with androgen deprivation responsiveness in patients with metastatic prostate cancer before endocrine therapy.

Significance of serum free prostate specific antigen in the screening of prostate cancer.

PURPOSE The significance of serum free prostate specific antigen (PSA) in the screening of prostate cancer was examined. MATERIALS AND METHODS A prospective clinical trial was conducted on 701 male volunteers 50 years old or older. Serum free PSA was determined and biopsies were performed if PSA was greater than 4 ng./ml. or if digital rectal examination was suspicious for cancer. RESULTS Of the men 187 (27%) had a PSA of greater than 4 ng./ml. (11%) and/or a suspicious digital rectal examination (19%). Of 116 biopsies performed in the 701 men cancer was detected in 13 (1.9%). PSA detected more tumors (12 of 13, 92%) than digital rectal examination (9, 69%). Receiver operating characteristic analysis showed that the optimal free PSA-to-PSA ratio (free PSA ratio) was 12%. The positive predictive value for cancer according to PSA with free PSA ratio (50%, 10 cancers in 20 biopsies) was significantly greater (p = 0.0473) than that according to PSA alone (24%, 12 cancers in 50 biopsies), which indicated that 30 of 50 biopsies were avoided with only 2 cancers missed when PSA and free PSA were used for biopsy indication. CONCLUSIONS Free PSA determination might eliminate unnecessary biopsies in men with a PSA of more than 4 ng./ml. with minimal missed cancers.

Value of reverse transcription polymerase chain reaction assay in pathological stage T3N0 prostate cancer.

We tested the ability of the nested reverse transcription polymerase chain reaction (RT‐PCR) assay to detect signs of biochemical recurrence of prostate cancer in the lymph nodes and peripheral blood of patients with pT3N0 prostate cancer.

Preoperative nested reverse transcription‐polymerase chain reaction for prostate specific membrane antigen predicts biochemical recurrence after radical prostatectomy

To assess the utility of the nested reverse transcription‐polymerase chain reaction (RT‐PCR) method for measuring prostate specific membrane antigen (PSM) and prostate specific antigen (PSA) in predicting serum PSA recurrence after radical prostatectomy.

Laparoscopic management of urachal remnants in adulthood

Background: The aim of this study was to investigate the outcome of laparoscopic excision of urachal remnants (LUR), and to compare the outcome with that of the traditional open excision of urachal remnants (OUR).

Detection of circulating MUC7‐positive cells by reverse transcription–polymerase chain reaction in bladder cancer patients

Abstract Background:  To determine whether MUC7 gene expression can be used as a bladder cancer marker in peripheral blood.

Comparisons of the Various Combinations of Free, Complexed, and Total Prostate–Specific Antigen for the Detection of Prostate Cancer

Objectives: We compared the ability of three prostate–specific antigen (PSA) ratios – free–to– total PSA ratio (fPSA/tPSA), free–to–complexed PSA ratio (fPSA/cPSA), and complexed–to–total PSA ratio (cPSA/tPSA) – to distinguish prostate cancer from benign prostatic hyperplasia (BPH).Methods: We tested 258 consecutive patients who underwent transrectal ultrasound–guided prostate needle biopsy because of an abnormal digital rectal examination or a Tandem–R PSA of >4.1 ng/ml. Free PSA (fPSA) and total PSA (tPSA) were measured by Tandem–R assay. α1–Antichymotrypsin–complexed PSA (cPSA) was measured by Markit–M PSA–ACT assay.Results: Of the 258 patients, 204 had BPH, and 54 had prostate cancer. The specificity at 96% sensitivity for fPSA/tPSA, fPSA/cPSA, and cPSA/tPSA was 23, 25, and 33%, respectively. Of 162 patients with tPSA between 4.1 and 10.0 ng/ml, 132 had BPH and 30 had prostate cancer. The specificity at 96% sensitivity for f/tPSA, f/cPSA and c/tPSA was 32, 44, and 41%, respectively. There was no significant difference in the area under the receiver–operating characteristic curves among fPSA/tPSA, fPSA/cPSA, and cPSA/tPSA in the overall PSA range or in tPSA between 4.1 and 10.0 ng/ml.Conclusion: fPSA/tPSA, fPSA/cPSA, and cPSA/tPSA did not differ in their ability to distinguish prostate cancer from BPH.